Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin from
            <i>Mycoplasma pneumoniae</i>

Becker, Argentina; Kannan, Thirumalai R; Taylor, Alexander B.; Pakhomova, Olga N.; Zhang, Yanfeng; Somarajan, Sudha R.; Galaleldeen, Ahmad; Holloway, S.; Baseman, Joel B.; Hart, P. John

doi:10.1073/pnas.1420308112

Cited by 67 publications

(73 citation statements)

References 50 publications

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“…Recently, CARDS toxin was recognized by Kannan et al., which is involved in the pathophysiology of Mp disease. The toxin binds to human surfactant protein A and annexin A2 on airway epithelial cells and is internalized, leading to a range of pathogenetic events . Other factors are well known for their harmful effects via oxidative stress.…”

Section: Pathogenesis Of Mp Pneumoniamentioning

confidence: 99%

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Mycoplasma pneumoniae infection: Basics

Saraya

2017

J of Gen and Family Med

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Mycoplasma pneumoniae (Mp) is one of the leading causes of community‐acquired pneumonia and can cause a number of extrapulmonary manifestations in the absence of pneumonia. In this regard, primary care physicians should know how to suspect, diagnose, and manage patients with Mp infection. This review gives a general overview of the basic clinical aspects of Mp infection with special reference to pneumonia, which will help further understanding of the disease.

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Section: Pathogenesis Of Mp Pneumoniamentioning

confidence: 99%

“…The toxin binds to human surfactant protein A and annexin A2 on airway epithelial cells and is internalized, leading to a range of pathogenetic events. 33 Other factors are well known for their harmful effects via oxidative stress.…”

Section: Extrapulmonary Manifestationsmentioning

confidence: 99%

Mycoplasma pneumoniae infection: Basics

Saraya

2017

J of Gen and Family Med

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“…pneumoniae of the community acquired respiratory distress syndrome toxin, an ADP ribosylating toxin with vacuolating activity (16).…”

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confidence: 99%

MIB–MIP is a mycoplasma system that captures and cleaves immunoglobulin G

Arfi

Minder

Primo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mycoplasmas are "minimal" bacteria able to infect humans, wildlife, and a large number of economically important livestock species. Mycoplasma infections include a spectrum of clinical manifestations ranging from simple fever to fulminant inflammatory diseases with high mortality rates. These infections are mostly chronic, suggesting that mycoplasmas have developed means to evade the host immune response. Here we present and functionally characterize a two-protein system from Mycoplasma mycoides subspecies capri that is involved in the capture and cleavage of IgG. The first component, Mycoplasma Ig binding protein (MIB), is an 83-kDa protein that is able to tightly bind to the Fv region of a wide range of IgG. The second component, Mycoplasma Ig protease (MIP), is a 97-kDa serine protease that is able to cleave off the VH domain of IgG. We demonstrate that MIB is necessary for the proteolytic activity of MIP. Cleavage of IgG requires a sequential interaction of the different partners of the system: first MIB captures the IgG, and then MIP is recruited to the MIB-IgG complex, enabling protease activity. MIB and MIP are encoded by two genes organized in tandem, with homologs found in the majority of pathogenic mycoplasmas and often in multiple copies. Phylogenetic studies suggest that genes encoding the MIB-MIP system are specific to mycoplasmas and have been disseminated by horizontal gene transfer. These results highlight an original and complex system targeting the host immunoglobulins, playing a potentially key role in the immunity evasion by mycoplasmas.

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“…The N-terminal region or Domain 1, which is homologous to the pertussis toxin S1 subunit (PTX) from Bordetella pertussis, includes the catalytic ADP-ribosylating region (Becker et al, 2015;Kannan et al, 2005;Kannan et al, 2014). The C-terminal region of CARDS toxin (Domains 2 and 3) contains the cell receptor binding and vacuolating activities .…”

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confidence: 99%

Disulfide bond ofMycoplasma pneumoniaecommunity‐acquired respiratory distress syndrome toxin is essential to maintain the ADP‐ribosylating and vacuolating activities

Balasubramanian

Pandranki

Maupin

et al. 2019

Cellular Microbiology

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Mycoplasma pneumoniae is the leading cause of bacterial community-acquired pneumonia among hospitalised children in United States and worldwide. Communityacquired respiratory distress syndrome (CARDS) toxin is a key virulence determinant of M. pneumoniae. The N-terminus of CARDS toxin exhibits ADP-ribosyltransferase (ADPRT) activity, and the C-terminus possesses binding and vacuolating activities.Thiol-trapping experiments of wild-type (WT) and cysteine-to-serine-mutated CARDS toxins with alkylating agents identified disulfide bond formation at the amino terminal cysteine residues C230 and C247. Compared with WT and other mutant toxins, C247S was unstable and unusable for comparative studies. Although there were no significant variations in binding, entry, and retrograde trafficking patterns of WT and mutated toxins, C230S did not elicit vacuole formation in intoxicated cells. In addition, the ADPRT domain of C230S was more sensitive to all tested proteases when compared with WT toxin. Despite its in vitro ADPRT activity, the reduction of C230S CARDS toxin-mediated ADPRT activity-associated IL-1β production in U937 cells and the recovery of vacuolating activity in the protease-released carboxy region of C230S indicated that the disulfide bond was essential not only to maintain the conformational stability of CARDS toxin but also to properly execute its cytopathic effects.

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Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin from Mycoplasma pneumoniae

Cited by 67 publications

References 50 publications

Mycoplasma pneumoniae infection: Basics

Mycoplasma pneumoniae infection: Basics

MIB–MIP is a mycoplasma system that captures and cleaves immunoglobulin G

Disulfide bond ofMycoplasma pneumoniaecommunity‐acquired respiratory distress syndrome toxin is essential to maintain the ADP‐ribosylating and vacuolating activities

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